a. Cortex - lymph nodules, where lymphocytes, especially B-cells, proliferate, expanding B-cell clones, frequently separated from each other by connective tissue septa. Sinuses pass around the nodules.

b. Subcortical - this region is also called the paracortical and diffuse cortical area. It is a "T" dependent zone and is the site of lymphoblast formation in immune responses involving both T & B cells. Blasts of the B-cell variety migrate into nodules to form germinal centers. High endothelial (post-capillary) venules express selectin on their luminal surface that binds T-cells and facilitate their migration out of the vessel.

c. Medulla - medullary cords of lymphoid tissue containing plasma cells are separated from connective tissue trabeculae by medullary sinuses.

a. Framework - dense c.t. capsule and irregular septa and trabeculae. Sinuses lined by loosely arranged endothelial cells are closely applied to these structures.

b. Vasculature - arteries and larger veins follow c.t. trabeculae which radiate from the hilus through the medulla. In the medulla, the veins enter the trabeculae from the medullary cords. As the trabeculae approach or reach the cortex, small arterioles leave the trabeculae and break up into a capillary bed in the lymphoid tissue of the cortex. Turning toward the hilus, the capillaries open into specialized post-capillary venules (cuboidal endothelium) in the subcortical region. The height of the post-capillary endothelium is related to the intensity of T-cell involvement in an immune response. These venules continue into the medullary cords, joining to form veins as they approach the hilar trabeculae. Lymphocytes (T-cells) leave the blood as it passes through the post-capillary venules.

c. Lymphoid tissue - a reticulum of reticular fibers and associated reticular cells with lymphoid cells filling the spaces. In lymph nodes, lymph sinuses surround both cortical and medullary lymphoid tissue. Molecular and cellular communication between the sinuses and lymphoid tissue is rapid.

d. Sinuses - narrow intermediate (cortical) sinuses convey lymph from the subcapsular sinuses to the broad, tortuous medullary sinuses. Collagen and reticular fibers covered by stellate endothelial cells, criss-cross the sinuses. Macrophages cling to these, and participate in trapping foreign particles carried by the lymph. Lymphocytes enter the lymph as it flows through the lymph node.

a. Capsule and trabeculae - prominent c.t. capsule contains some smooth muscle and elastic fibers. Trabeculae extend into the organ.

b. White pulp - accumulations of lymphoid tissue usually surrounding a "central" artery. It participates in the immune responses of the body. Marginal zone macrophages differ from the red pulp macrophages and appear to be especially adapted to react with the B-cells of the nodules.

c. Red pulp - consists of venous sinuses and pulp cords. The latter consists of a reticular network containing macrophages, reticular cells and blood cells.

Vascular c.t. trabeculae radiating from the hilus, carry both veins and arteries, but arteries soon leave the trabeculae and become surrounded by white pulp. The white pulp, consisting of a periarterial sheath (mostly T-cells), is enlarged at intervals to form lymph nodules (splenic nodules) on one side of the central artery. Small branches of the central artery supply the white pulp, the venous drainage being by way of the red pulp. As the central artery leaves the white pulp, it forms several branches, the penicillar arteries. Some of the capillaries which arise from the penicillar artery are surrounded by a special sheath (ellipsoid) of reticular fibers and macrophages. Directly or indirectly via pulp cords (the indirect route is most prominent), the blood enters rather large venous sinuses lined by very elongated endothelial cells, with narrow slits between, through which the blood leaves the red pulp to enter the venous system. In either case, blood percolates through the red pulp, where macrophages remove effete blood cells. The venous sinuses empty into veins which lead to trabecular veins.

a. Regions - the cortex consists of a peripheral zone of closely packed lymphocytes, which do not form nodules, capping over numerous protrusions of the less cellular medulla.

b. Framework and stroma - the thin c.t. capsule and septa provide external support. Internally, the reticular network characteristic of lymphoid tissue elsewhere is replaced by cytoplasmic processes of epithelioreticular cells. These cells form a thin layer just under the capsule and around blood vessels contributing to a blood-thymus barrier. They are a major component of the medulla but less in the cortex. They are the source of the hormone, thymosin. Epithelio-reticular cells do not arise from mesoderm as do the reticular cells of other lymphoid organs, but instead come from endoderm (pharyngeal pouch epithelium).

c. Vasculature - arteries follow the c.t. septa to the cortico-medullary junction between lobules where arterioles enter the lobules. From arterioles in the C-M junction, capillaries enter the cortex, then turn back on themselves to empty into venules in the medulla. Many lymphocytes enter the blood stream through these venules. The medullary veins ultimately leave through c.t. septa accompanying the arteries. Reticuloepithelial cells, macrophages surrounding capillaries, and capillary endothelial cells with zonula occludens, make an effective blood-thymus barrier.

1. Blood - circulating lymphocytes about 15% are B-cells

2. Nodules - B-cells are localized to the small lymphocyte cap of nodules and the dark region of reaction centers.

3. Lymph nodes and spleen - B-cells are concentrated in cortical nodules of lymph nodes and at the periphery of the periarterial lymphoid sheath in the spleen.

1. Surface - immunoglobulin molecules (IgD or IgM) are distributed on the outer surface of B-cells. These are specific for a single antigen. In the presence of antigen, they become aggregated to one side (cap) and are then ingested by the cell. These events appear to trigger activation.

2. Activation or blastogenic transformation

1. Memory cells - many small lymphocytes bearing Ab specific for the Ag. These cells "seed" lymphoid tissues throughout the body.

2. Effector cells - medium to large lymphocytes and plasma cells producing antibody. These lymphocytes are distributed to the GI lamina propria and lymphoid organs, where they become plasma cells.

a. Directly - T-cells make direct contact with the foreign cells and release factors (perforin) that punch holes their membrane so that they are lysed.

b. Indirectly - cells release lymphokines, some of which are: